维生素D衍生物的合成及烯丙位氧化的优化

Synthesis of Vitamin D Derivatives and Optimization of Allylic Oxidation

以维生素D2为原料,经过二氧化硫异构化、叔丁基二甲基氯硅烷进行羟基保护、碳酸氢钠/乙醇脱去二氧化硫、烯丙位氧化最终合成维生素D2衍生物5-（叔丁基-二甲基-硅烷氧基）-2-亚甲基-3-{2-[7a-甲基-1-（1,4,5-三甲基-己-2-烯基）-八氢-茚-4-亚基]-亚乙基}-环己醇,并改进后处理方法使反应前后产物较为稳定。考察反应温度、氧化剂和助氧化剂的用量、溶剂种类和体积配比、不同助氧化剂下的不同反应时间对烯丙位氧化产率的影响。结果表明,最佳反应条件为V（二氯甲烷）∶V（甲醇）∶V（1,2-二氯乙烷）=2∶1∶1,温度为50℃,n（底物）∶n（二氧化硒）∶n（助氧化剂）=1∶1∶4且N-甲基吗啉-N-氧化物为助氧化剂,此时烯丙位氧化的产率达65.1%,4步反应总收率为60.5%。

Using Vitamin D2 as a starting material,Vitamin D2 is isomerized by sulfur dioxide. Hydroxyl is protected by tert-butyldimethylsilyl chloride.Sulfur dioxide is stripped by sodium bicarbonate/ethanol.And material is allylic oxidized to finally synthesize Vitamin D2 derivative that is 5-（ butyl-dimethyl）-silanyloxy）-2-methylene-3-{ 2-[7 a-methyl-1-（ 1,4,5-trimethyl-hex-2-enyl）-octahydro-indene-4-subunits]-ethylidene}-cyclohexanol. And the post-treatment method is improved to make the product more stable before and after the reaction.The effects of reaction temperature,the amount of oxidant and co-oxidizing agent,solvent type and volume ratio,different reaction time of different co-oxidants on the yield of allylic oxidation were investigated.The results show that when the solvent is V（ dichloromethane） ∶ V（ methanol） ∶ V（ 1,2-dichloroethane） = 2 ∶ 1 ∶ 1,reaction temperature 50 ℃,n（ substrate） ∶ n（ selenium dioxide） ∶ n（ co-oxidizing agent） = 1 ∶1 ∶4 and N-methylmorpholine-N-oxide as co-oxidizing agent is the best reaction condition,so that the yield of allylic oxidation reached 65. 1%,the total yield of four steps reached 60. 5%.